Long-term Effects of Neonatal Treatment with Progesterone, Alone and in Combination with Estrogen, on the Mammary Gland and Reproductive Tract of Female BALB/cfC3H Mice

Neonatal female mice of the BALB/cfC3H strain were given 5 daily injections of 17beta-estradiol and progesterone alone and in combination, beginning within 36 hr after birth. Half of the mice in each group were ovariectomized at 40 days of age, and all were killed at tumor age of at 12 months of age. Mice receiving progesteron (100 mug daily) alone showed ovary-dependent persistent vaginal cornification. When neonatal progesterone and estradiol were given concurrently, the occurrence of persistent vaginal cornification was significantly lower than in mice receiving neonatal estradiol treatment alone. Progesterone alone produced hyperplastic downgrowths and lesions of both vaginal and cervical epithelia, but to a lesser degree than occurred in mice treated neonatally with estrogen. When progesterone was given concurrently with 17beta-estradiol, the incidence of lesions was lower but their severity was greater. The low doses of 17beta-estradiol and progesterone each resulted in an earlier age of onset and a higher incidence of mammary tumors; this also occurred after both combined estrogen-progesterone treatments. In treated mice ovariectomized on Day 40, normal mammary development did not occur and mammary tumors failed to appear, regardless of neonatal treatment. The data indicate a clear effect of neonatal progesterone exposure on both the genital tract and the mammary apparatus of female mice.